1. Field of the Invention
This invention relates to a general process for producing N-arylated amine compounds, and more particularly to a general process for the formation of N-arylated amine compounds from amines and an arylating compound using transition metal catalysts containing P(t-Bu).sub.3 as a ligand.
2. Brief Description of the Related Art
N-Aryl amines are important substructures in natural products and industrial chemicals, such as pharmaceuticals, dyes, and agricultural products. The palladium-catalyzed amination of aryl halides has become an important method for the synthesis of arylamines found in pharmaceuticals, materials with important electronic properties, and ligands for early metal catalysts. Because of the importance of this synthetic method, approaches that provide high turnover numbers, fast reaction rates, high functional group compatibility, and increased scope of the aromatic C--N bond formation are highly desired.
It would be advantageous to prepare N-aryl compounds from arylating compounds such as aryl halides and/or aryl sulfonates because aryl halides are generally inexpensive and readily available, while aryl sulfonates are easily prepared from phenols. However, to date, methods of producing many types of N-aryl compounds are inefficient or economically unattractive.
In one example, workers at Tosoh Company reported that the catalysts containing the P(t-Bu).sub.3 ligand provided high turnover numbers for the formation of aryl piperazines with excess ligand (4:1 ratio of P(t-Bu).sub.3 ligand to Pd) at 120.degree. C. (Nishiyama, N. et al., Tetrahedron Lett. 39:617-620 (1998); Yamamoto, T. et al., Tetrahedron Lett. 39:2367-2370 (1998)). However, the high temperatures of this reaction scheme make it unattractive for commercial use.
In another example, Hartwig et al. have shown that a sterically hindered alkylphosphine prepared in one step allows for room temperature amination of aryl halides and that another commercially available, sterically hindered alkylphosphine allows for the reaction of aryl chlorides with primary alkylamines under mild conditions (Hamann, B. C. and Hartwig, J. F., J. Am. Chem. Soc. 120:7369-7370 (1998)). It has also been reported recently that a P,N ligand containing a biphenyl backbone, which is prepared in three steps, generates a catalyst that leads to examples of room temperature amination chemistry with aryl bromides and room temperature Suzuki chemistry with aryl chlorides (Old, D. W. et al. J. Am. Chem. Soc. 120:9722-9723 (1998)). However, the multistep nature of the synthesis of this ligand makes it less attractive for commercial purposes.
In view of the above, a need exists for a general and efficient process of synthesizing N-aryl compounds from readily available arylating compounds and commercially available catalysts. The discovery and implementation of such a method would simplify the preparation of commercially significant organic N-aryl amine compounds and would enhance the development of novel polymers and pharmacologically active compounds. The present invention is believed to be an answer to that need.